Steinmetz R, Brown N G, Allen D L, Bigsby R M, Ben-Jonathan N
Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis 46202, USA.
Endocrinology. 1997 May;138(5):1780-6. doi: 10.1210/endo.138.5.5132.
Environmental estrogens (xenoestrogens) are a diverse group of chemicals that mimic estrogenic actions. Bisphenol A (BPA), a monomer of plastics used in many consumer products, has estrogenic activity in vitro. The pituitary lactotroph is a well established estrogen-responsive cell. The overall objective was to examine the effects of BPA on PRL release and explore its mechanism of action. The specific aims were to: 1) compare the potency of estradiol and BPA in stimulating PRL gene expression and release in vitro; 2) determine whether BPA increases PRL release in vivo; 3) examine if the in vivo estrogenic effects are mediated by PRL regulating factor from the posterior pituitary; and 4) examine if BPA regulates transcription through the estrogen response element (ERE). BPA increased PRL gene expression, release, and cell proliferation in anterior pituitary cells albeit at a 1000- to 5000-fold lower potency than estradiol. On the other hand, BPA had similar efficacy to estradiol in inducing hyperprolactinemia in estrogen-sensitive Fischer 344 (F344) rats; Sprague Dawley (SD) rats did not respond to BPA. Posterior pituitary cells from estradiol- or BPA-treated F344 rats strongly increased PRL gene expression upon coculture with GH3 cells stably transfected with a reporter gene. Similar to estradiol, BPA induced ERE activation in transiently transfected anterior and posterior pituitary cells. We conclude that: a) BPA mimics estradiol in inducing hyperprolactinemia in genetically predisposed rats; b) the in vivo action of estradiol and BPA in F344 rats is mediated, at least in part, by increasing PRL regulating factor activity in the posterior pituitary; c) BPA appears to regulate transcription through an ERE, suggesting that it binds to estrogen receptors in both the anterior and posterior pituitaries. The possibility that BPA and other xenoestrogens have adverse effects on the neuroendocrine axis in susceptible human subpopulations is discussed.
环境雌激素（外源性雌激素）是一类能模拟雌激素作用的多种化学物质。双酚A（BPA）是许多消费品中使用的塑料单体，在体外具有雌激素活性。垂体催乳素细胞是一种成熟的雌激素反应细胞。总体目标是研究双酚A对催乳素释放的影响并探索其作用机制。具体目标如下：1）比较雌二醇和双酚A在体外刺激催乳素基因表达和释放的效力；2）确定双酚A在体内是否增加催乳素释放；3）检查体内雌激素作用是否由垂体后叶的催乳素调节因子介导；4）检查双酚A是否通过雌激素反应元件（ERE）调节转录。双酚A增加了垂体前叶细胞中催乳素基因的表达、释放和细胞增殖，尽管其效力比雌二醇低1000至5000倍。另一方面，在对雌激素敏感的Fischer 344（F344）大鼠中，双酚A在诱导高催乳素血症方面与雌二醇具有相似的功效；Sprague Dawley（SD）大鼠对双酚A无反应。用报告基因稳定转染的GH3细胞与经雌二醇或双酚A处理的F344大鼠的垂体后叶细胞共培养后，催乳素基因表达强烈增加。与雌二醇类似，双酚A在瞬时转染的垂体前叶和后叶细胞中诱导ERE激活。我们得出以下结论：a）双酚A在遗传易感性大鼠中模拟雌二醇诱导高催乳素血症；b）雌二醇和双酚A在F344大鼠中的体内作用至少部分是通过增加垂体后叶催乳素调节因子活性来介导的；c）双酚A似乎通过ERE调节转录，这表明它与垂体前叶和后叶中的雌激素受体结合。文中讨论了双酚A和其他外源性雌激素对易感人群神经内分泌轴产生不利影响的可能性。
